Peripheral Brachytherapy of Protruding Conformable Organs

ABSTRACT

A system for and method of applying non-invasive brachytherapy to a targeted volume within a protruding organ of a patient, employs an applicator constructed so as to be positioned relative to the organ so that an enhanced dose of divergent radiation is deliverable from at least two locations at or very near the periphery of the organ transcutaneously to the targeted volume of the protruding organ from at least two directions so that a higher dose is delivered to the targeted volume than to tissue surrounding the targeted volume. The treatment planning, and image guidance techniques are also described.

RELATED APPLICATION

This application is a continuation of U.S. application Ser. No.11/354,620, filed Feb. 15, 2006, which is a non-provisional applicationof U.S. Provisional Application No. 60/653,191, filed Feb. 15, 2005.Each of the above-mentioned applications is incorporated herein byreference in its entirety as though fully set forth herein.

FIELD OF DISCLOSURE

The disclosure generally relates to brachytherapy, and more specificallyto non-invasive devices for and methods of providing peripheralbrachytherapy to protruding organs.

BACKGROUND OF THE DISCLOSURE

Various forms of brachytherapy have been practiced since the time ofdiscovery of radioactivity by Mme. Curie. Brachytherapy, from the Greekroot meaning “from a short or near distance” is a term typically used todescribe the placement of one or more radioactive sources within tissueor in a body lumen or body cavity to deliver a therapeutic dose to atumor or tumor bed near the source. Brachytherapy as it is practicedtoday includes several varieties of invasive treatment. Interstitialbrachytherapy includes the step of placing the radioactive source orsources within the tissue (e.g. prostate gland). Intra-luminalbrachytherapy includes introducing the source through an anatomicallumen (e.g. vascular). Intra-cavitary brachytherapy is performed byplacing the radioactive source inside a naturally occurring cavity nearthe cancerous tissue (e.g. cervical cancer, or orbital cavity forintra-ocular melanoma), or a man-made cavity created during surgery(e.g. breast lumpectomy or other tumor beds). Various brachytherapyapplicators are known and used in invasive procedures.

A surface applicator, including structure for defining a series ofparallel lumens for receiving high dose radiation (HDR) sources, hasbeen used for treatment of surface lesions, skin cancer or during opensurgeries for tissues which are easily accessed. (See, for example, theVarian catalog at www.varian.com/obry/pdf/vbtapplicatorcatalogue.pdf,page 113). This applicator is not designed to treat a deep seated tumoror tumor bed, however.

Cash et al. (U.S. Pat. No. 6,560,312) discloses a technique ofperforming radiosurgery on a human body using teletherapy. The techniqueincludes accumulating non-converging radiation fields to reach atherapeutic dose. The teletherapy design of Cash et al. is based upon apredetermined distribution of remote x-ray sources to create a volumewhere multiple beams intersect within the human body. It relies on theability to align remote sources located on one platform to treat alesion within a patient who is positioned on a separate platform. Thisapproach has major limitations where relative positioning of the sourcesmust be carefully maintained in order to provide precise lesiontracking, particularly when patient motion, such as that associated withbreathing, can cause misalignments during treatment (as for example,when the patient is being treated for breast cancer).

Sundqvist (U.S. Pat. No. 4,780,898) and Leskell (U.S. Pat. Nos.5,528,651, 5,629,967 and 6,049,587) collectively describe a teletherapysystem sold under the trademark “GammaKnife”, and assigned to ElektaInstrument AB. The system is used to treat inoperable fine brain tumorsby exposing a localized point within the brain of the patient. GammaKnife relies on rigidly immobilizing the head of a patient by attachinga “helmet” directly to the skull, and simultaneously exposing the braintissue to sources of radiation from multiple angles. Each source iscollimated, emitting converging radiation beamlets that target a singlefocus point. By careful alignment of each of the source beamlets orlines of treatment, the Gamma-Knife system is able to build up theradiation field to therapeutic levels at the location of the target. Thedesign is useful for treatment of very fine (point) lesions and requirescareful orientation of each beamlet or line of treatment.

GENERAL DESCRIPTION OF THE DRAWINGS

In the drawings:

FIG. 1 is a perspective view of one embodiment of an applicator used forbrachytherapy treatment of the breast in accordance with the principlesdescribed herein;

FIG. 2 is a cross section taken through the cup of the applicator shownin FIG. 1 and supporting the breast under treatment;

FIG. 3 is a perspective view of another embodiment of an applicator usedfor brachytherapy treatment of the breast in accordance with theprinciples described herein;

FIG. 4 is a cross section taken through the cup of the applicator shownin FIG. 3 for supporting the breast under treatment;

FIG. 5 is a cross section of a portion of an applicator includingattenuators having embedded sources to facilitate directional deliveryof radiation from each of the sources;

FIGS. 6A-6D illustrate an embodiment of a sequence of steps forproviding brachytherapy to the breast using a parallel plate applicatorand a dedicated imaging mammography system;

FIG. 7 is a cross-section of an example of a dose map overlaid onto a CTimage from a prototype bra-style applicator mounted on a phantom to showthe isodose distribution to the breast using a “lampshade” style HDRcatheter pattern;

FIGS. 8A-8B illustrates an example of finite element analysis (FEA) ofthe field distribution from a single field shaping cell of anapplicator, and a series of field shaping cells placed within the topand bottom plates of a typical parallel plate applicator, respectively;

FIGS. 9A and B represents a typical program flowchart indicating primarycalculations to be performed, major inputs (both static and dynamic) andmajor decision making paths in a typical treatment sequence;

FIG. 10 is an illustration of multiple field shaping cells used tocontrol the relative dose of radiation to the skin vs. dose to thecenter of the target volume;

FIGS. 11A and B illustrate two examples of the orientation of the fieldshaping cells used to control the exposure of tissues to radiation;

FIG. 12 is a perspective schematic view of an example of a continuousfield shaping cell;

FIG. 13 is a perspective schematic view of an example of a singleconical field shaping structure/cell;

FIG. 14 is a perspective schematic illustration of an example of anapplicator using a robotic arm; and

FIGS. 15A-C are cross-sectional views showing the effects of positioninga source within a field shaping structure on the divergent shape of theradiation pattern emitted from the field shaping structure.

DETAILED DESCRIPTION OF THE DRAWINGS

The devices and methods described in this disclosure are particularlysuitable for treatment of a large, designated or targeted volume (on theorder of a few to tens of cubic cm, or greater) within a protrudingorgan, such as a breast, testicle, or penis. In one embodiment thedevices and methods require one or more divergent beams or patterns oftherapeutic radiation from one or more radiation sources placed withinan applicator supported relative to the surface of a protruding organ.It should be understood that as used herein, reference to a “source” or“sources”, in each instance, can mean either a single source adapted tobe configured and/or moved so as to radiate in more than one directiontoward the targeted volume, or a distribution of two or more sourcessimilarly adapted to be configured so as to radiate in more than onedirection, so as to concentrate more of the total exposable radiation inthe targeted volume, than in the surrounding tissue. The applicator isaffixed relative to the organ for each exposure by the source orsources, and provides a stable platform for receiving the radiationsource and delivering the dose to the designated volume independent oftarget movement (e.g., due to breathing cycle). The definition of adesignated volume as well as the relative positioning of the source orsources in the applicator can be correctly identified by imagingguidance techniques for proper alignment and monitoring of the delivereddose. In one application, the source(s) must be positioned within anarrow range of distances from the skin. Placing the source(s) too closeto the skin (e.g., less than about 3 mm) can cause excessive skinexposure; while placement farther than a few cm (e.g., 5 cm) away fromthe skin can result in the intensity of the dose falling off and thebrachytherapy becoming inefficient, and therefore insufficient andineffective. By proper source placement(s) relative to the targetedvolume during treatment, multiple divergent beams can be directed tooverlap or intersect solely in the targeted volume. This, in turn,results in the exposure fields being superpositioned within and thusprovide the therapeutic dose to the targeted volume, while the portionof the volume that is not exposed to the intersection of the divergentbeams receives a sub-therapeutic dose.

The disclosure also describes the design and utilization of anon-invasive brachytherapy technique where a distributed radiationsource pattern is created by using one or more sources. The source orsources can include, but not limited to, one or more isotopes, one ormore discrete sources, and/or one or more generators of ionizingradiation. During treatment, the portions of a single source or themultiple sources that provide the therapeutic dose are preferablydistributed in or sequentially moved to predetermined fixed positions ata close predetermined distance to the skin around a protruding organ,and moved and/or arranged so that a prescribed therapeutic dose isdelivered to the targeted tumor or tumor bed within the organ. Imagingguidance is preferably, but not necessarily, used to locate and definethe designated target volume within the organ to which the radiationwill be delivered. The prescribed dose delivered to the designatedvolume can be determined, for example, by calculating the totalcumulative or sum of the superpositioned lower doses respectivelydelivered to the designated volume from the distributed positionsarranged around the targeted tissue. Alternatively, computer simulationtechniques can be employed to determine the superpositioned orsuperimposed (cumulative) dose delivered to the desired volume takinginto account the shape, size, volume of the designated targeted tissueand its location and distance from the skin.

A protruding deformable organ, such as the breast, offers a uniquegeometry for radiation therapy from the periphery. It allows anon-invasive applicator to be designed (and accordingly facilitate aprocedure for treatment) such that the applicator may, in the case of abreast, for example, modify the shape of the breast, and allow a sourceor sources of radiation to surround, or be positioned at two or morelocations at the periphery of the organ, so as to allow for a pattern ofoverlapping, intersecting beams of diverging radiation from two or moredirections/angles to increase the cumulative dose to the inner targetedtissue, or designated volume, within the organ, and fix the distance ofthe source(s) at each of the locations from which each beam of divergingradiation is directed. This overlap within the designated volume allowsthe source, or each of the plurality of sources, to deliver loweraverage doses to the intervening tissue from each of a plurality ofpositions, while delivering a higher dose to the targeted tissue thanotherwise provided when only a single source of radiation is used. Thus,the approach disclosed herein, which in the case of the treatment ofbreast cancer we term the Peripheral Brachytherapy of the Breast (PBB)concept, has the benefit of limiting the dose to untargeted, otherwisehealthy, tissue facing each radiation source location. This is notpossible with teletherapy sources or beams of radiation available fromconventional radiotherapy. The limited penetration from the radiationsource(s) advocated in this disclosure along with the geometry of andthe relative proximity of the applicator combine to limit the doses tothe underlying, adjacent, otherwise healthy tissues surrounding thetargeted tissue, while delivering a therapeutic dose to the targetedvolume within that organ. The higher dose can be created by variousmeans, all of which involve effectively surrounding (or at leastpositioning at select locations around the periphery of) the deformableprotruding organ. The source(s) are preferably positioned inthree-dimensional space so that the source at each position is apredetermined, relatively fixed position from the targeted volume, andthe fields generated at each source location constructively add withinthe targeted volume, thus, collectively producing the therapeutic doselevels at that location. A source may be placed at each of several ofthe locations at the same time and/or a source may be moved to each ofseveral positions over time during treatment. This disclosurecontemplates that the source or sources of radiation provide pointsources (substantially one dimensional), line (not necessarily straight)sources (two dimensional) and/or broad planar (not necessarily flat, butextending in three dimensions) sources so as to create the overlappingradiation pattern that provides accumulated dose at the targeted volume.The radiation source(s) can include, but are not limited to,radioisotopes or generators of ionizing radiation (x-ray or electronsources).

The embodiments of the method and system disclosed herein areparticularly useful for brachytherapy of a breast carcinoma following alumpectomy where the cancerous breast tissue has been surgicallyexcised, although it should be appreciated that other applications canbe provided without undue experimentation. Following a lumpectomy, toprevent local recurrence, there is a need to expose the tumor bed toradiation to “sterilize” the field and destroy pre-cancerousmicro-inclusions that may still exist near the original site that wouldotherwise result in a local failure. Typical brachytherapy dosesdelivered to the breast following lumpectomy have ranged from about 10Gyto about 50Gy. The specific dose depends on the dose rate, fractionationschedule and the duration of therapy, nature of the original growth,mono versus boost therapy, as well as host of other factors which willbe evident to one skilled in the art. A typical target for partialbreast brachytherapy is a volume extending from about 2 cm beyond thelumpectomy (excision cavity) margin. Using the presently disclosedPeripheral Brachytherapy of the Breast (PBB) concept, one can deliver asub-therapeutic dose to substantially the entire breast and atherapeutic dose to the target volume within the breast. The prescribedtherapeutic dose to the typical designated volume of the breast isusually in the range from about 15Gy to about 40Gy. The therapeutic dosedepends, among other factors, on the duration of radiotherapy, where theshorter the duration of radiotherapy the lower the dose. The primaryalternative (the current “standard of care”) is total breast irradiationby an external beam that is typically delivered in 5 to 7 weeks withdaily doses of about 1.8Gy, for a total dose of about 45Gy.

Generally accepted practice is that radiation therapy for breast canceris expected to be completed within 60 days, which is the maximumexpected duration for the PBB approach, although the period could varybeyond 60 days. More typically, using the PBB approach, the treatment isexpected to be delivered from about 2 days to about 10 days.

In accordance with the disclosed system and technique, peripheral breastbrachytherapy can be performed with the patient in any one of manydifferent positions. The patient may be treated, for example, whilelying in a supine or prone position. In the prone position, specialtables may be used. The tables can each include, for example, a properlypositioned hole or aperture for receiving the breast, so the breast canhang freely by the force of gravity. Alternatively, the patient may betreated while standing up or sitting down. The organ, especially whentreating the breast, may be conformed, or fitted within a confined spaceso as to ensure a fixed relationship between the position of the targetvolume and the position(s) of the source(s) during treatment. Varyingthe patient's orientation or movement of the target volume duringtreatment, relative to the source(s) relative to the treatment andimaging system, or movement of the target volume relative to thesource(s), will impact the ability to target and treat certainpredetermined volumes within the breast, as well as increase stray dosesto other organs and tissue. Thus, the positioning and orientation of thepatient, and whether the breast is confined during treatment mayactually depend in part on the location of the targeted volume.

For treatment of a conformable protruding organ like the breast, thesource(s) of radiation can be placed in a special applicator. Theapplicator, when supported relative to a conformable organ, willpreferably fix the shape of the organ relative to the source(s) duringtreatment, and provide a stable platform that delivers a constantradiation field independent of the body motion generally, or organmotion specifically, due, for example, to the breathing cycle. Theapplicators can be designed to either conform to the shape of, orsurround, the protruding organ thus allowing for the secure placement ofthe source(s) at the periphery of the organ in close proximity to itssurface. Alternately, the applicators may include a cavity for receivingthe organ, and may be made of a rigid material and rigid geometry suchthat the protruding organ is forced to take the shape of and thusconform to the shape of the cavity within the rigid applicator. Theapplicators further preferably include cells, pockets, recesses, and/orlumens for the insertion and movement and/or attachment of each sourceof radiation at the prescribed positions of treatment.

Compression plates are commonly used in mammography procedures. Thecompressed breast presents a flat uniform tissue mass and is easier toradiographically image for identification of calcification or cancerouslesions. Similarly, compressed breast tissue presents a more uniformtarget for radiotherapy. The present disclosure includes a method ofcompressing the breast between two plates to present a uniform mass forimaging and radiotherapy. In particular the orientation of thecompression can be altered to image and irradiate tissue from differentangles. The compression of the breast tissue , due to its deformablenature, causes the organ to spread laterally and thus can reduce theamount of normal tissue between the treatment plates and the designatedvolume. This can cause the dose to the normal tissue of the breast to besubstantially reduced. Two orthogonal compression plate orientations ora plurality of compression plate orientation angles can be used toperform imaging and radiotherapy. In the process of using differentcompression plate orientations for radiotherapy, the dose to thedesignated volume is accumulated while the skin dose is divided betweendifferent points of entry, thus controlling the skin toxicity. Apreferred angle for both radiographic imaging and radiotherapy is thedirection perpendicular to the compression plate. Imaging at eachcompression plate orientation allows for targeting the radiation fieldto match the designated site.

An embodiment of the present disclosure is to irradiate the margins of alumpectomy cavity. Two compressions of the breast from two orthogonalplanes allow radiotherapy from 2 orthogonal planes and enables theaccumulation of dose to the designated target without exceeding thetoxicity limit of the skin. The apparatus that can provide compression,image registration and radiotherapy is part of the disclosure.

Thus the applicator may take the form of a set of applicator plates,either of which, or both may include the structure for housing a sourceor sources of radiation near the surface of the protruding organ. Theseplates are preferably disposed parallel to one another and may be usedto compress the protruding organ. The plates may also be curved suchthat they are designed to conform to the general shape of the organ soas to reduce any discomfort for the patient, yet still be able to pressagainst the organ so as to compress the organ into a desired shape, andfix the targeted volume relative to the source(s) positions duringtreatment. Further, the applicators can include an elastic, flexible orpliable structure for conforming to the organ and keeping the applicatorin intimate contact with the organ to deliver a constant and consistentdose from prescribed directions and distances to the targeted volume. Anadditional function of the applicator may include lifting and separatingthe protruding organ from the neighboring parts of the body so as tominimize stray radiation doses into those neighboring parts. Theapplicator is preferably placed in contact with, or communication to,the surface (periphery) of the protruding organ which is being treatedso as to fix the source(s) relative to the target volume at eachtreatment position. As a result, unlike conventional teletherapyapproaches, the delivery of radiation to the organ is unaffected by themotion of the patient, such as motion associated with breathing.

To minimize stray radiation doses (doses to any other untargeted tissue,organ or person), the applicator may additionally include an attenuatingor shielding outer layer. Typical attenuating and shielding layers aremade of high atomic number, dense materials, but the specific selectionof the attenuating material will depend upon the particular organ,radiation source and treatment plan. The applicator may include an innerlayer designed for direct contact with the skin which can control thedistance of the radiation source from the skin. The thickness of such aninner layer should reduce the intensity of the skin dose for thatportion of the organ facing the radiation source. The inner layer mayalso include high water content, and may include a water filled spongeand/or gel media or water-equivalent materials.

Additional attenuating materials, apertures and structures may beincorporated into the applicator such that they provide structure forcontrolling and thus determining the direction(s) of the exposure field.These field-shaping structures may include, for example, masks, bandsand/or sheaths of attenuating material, or grooves within an attenuatingmaterial into which the sources are placed. The structures can also bemade of field shaping cells for receiving radiation source material. Thefield shaping cells may be designed in such a way as to limit the sideexposure while providing the full exposure of, and thus define the shapeof the beam of radiation that is used to expose the tissues directly infront of the cell or set of cells. The design of these cells (includingthe height, aspect ratio, attenuator material, attenuator thickness)thus can be used to selectively shape the radiation exposure field.Where HDR applicators are used, the field-shaping cells may be includedand preferably placed along the path of the HDR lumen(s) so as tocoincide with the dwell positions of the sources.

Patient positioning and image guidance are important to precisely targetradiation to a designated volume within a protruding organ. In the caseof a breast, various imaging methods including, for example, x-rays(such as mammography or CT scanning), ultrasound, fluoroscopy, MRI, andportal imaging, may be used for imaging the tumor or tumor bed anddetermining the radiation targets. Similarly, different radiographic orultrasonic fiducials, such as implantable markers, skin tattoos andcontrast media are commonly used to mark the tumor bed (the margins of alumpectomy cavity). Image guidance is usually of vital importance forradiotherapy of the breast as the breathing cycle presents a movingtarget. The present disclosure describes an embodiment designed so as to(a) facilitate the positioning of radiation source(s) in an applicatorthat is/are mounted to the breast and (b) deliver constant radiation tothe designated volume within the breast independent of the breast tissuemovement during the breathing cycle.

The applicators may include one or more markers to facilitate alignmentof the applicator with either the protruding organ or the imagingsystem. The applicator markers are preferably designed so as to bevisible by any one or several common imaging technologies (depending onthe one used in a specific application). Further, the markers may betracked by dose planning software to act as an aid to the precisetargeting of the radiation field.

In one embodiment the applicator bra may include channels, lumens orenclosures for receiving larger source(s). For example, as shown inFIGS. 1 and 2 a bra 20 including support straps 22, the bra 20 includesone or more compartments 24 formed between an inner layer 26 and outerlayer 28, and constructed to receive one or more radiation sources 30.The sources can be planar, line or point (or similar structures)sources, as previously mentioned. The configuration of each compartment24 may vary according to the size of the breast and the size, shape anddistance below the skin of the target tissue. In this embodiment thesource can be incorporated into a plate, foil, fabric, sheet, wire orpoint (or other structure) source (a foil being shown in FIG. 2),suitably treated so as to provide the necessary radiation pattern. Theouter layer 28 should be constructed to attenuate X-rays, while theinner layer, contacting the skin should be transparent to X-rays.Alternatively an X-ray absorbent plate, sheet, foil or similar structurecan be included within each compartment between the source and the outerlayer 28.

In the case of the breast, the applicator may be in the form of abrassier, cup or a pouch. In one embodiment of the current disclosurethe applicator may be constructed to receive source(s) (such as the braor brassiere 40 as shown in FIGS. 3 and 4). The bra 40 facilitatestreatment of a breast compatible with an HDR afterloader. The braincludes a pair of cups 42 for supporting the breasts and supportingstraps 44 so that the bra can be comfortably worn by the patient when inuse. The cup 42 a used to support the breast under treatment alsoincludes separate internal lumen(s) or compartment(s) 46 for receivingsource(s) 48. In the embodiment of the applicator shown, the lumen isadapted to receive a carrier supporting one or more sources. The carrieris preferably, although not necessarily a catheter 50 onto or into whichat least one source is attached or inserted. As best seen in FIG. 4, thecup 42 a includes at least one outer layer 52 and at least one innerlayer 54, defining the lumen(s) or compartment(s) 56 there between. Thelumen or compartment shown in FIGS. 3 and 4 has a spiral configuration.It should be understood that the configuration of the lumen(s) orcompartment(s) can assume other configurations and geometric shapes toaccommodate the source(s). The patterns of the channels, lumens andenclosures may vary according to the size of the breast and the size,shape and distance below the skin of the target tissue. Typical patternsfor the lumens would include, for example, substantially straight orcurved channels extending in predetermined directions, such as form thebase toward the tip of the cup, spiral(s), multiple concentric circlesof increasing diameter or a series of lumens which outline a cone or atruncated cone (i.e., frusta-conical shape) of tissue contained within.Clearly, the specific configuration of the cup and the sources can bedesigned depending upon the particular application and treatment. Inthis configuration, the patterns of the lumens as well as the dwelltimes for the source will be determined according to the size of thebreast, the size and shape of the designated tissue within the organ andthe position of the target with respect to the surface of the organ. Theouter layer 52 is preferably made of a shielding material (for example,a fabric containing lead) to absorb, and therefore reduce or preventradiation emitting outwardly from the cup, while the inner layer 54 ispreferably made of a material, such as a fabric that is substantiallytransparent to the X-rays so as to allow the X-rays to be propagatedthrough the inner layer into the targeted volume of the treatedpatient's breast. Alternatively, a shielding (X-ray absorbent) plate,sheet, fabric or material (not shown) made be provided between the outerlayer 52 and the compartment or lumen. In this latter instance the outerlayer need not include an X-ray absorbent material. A suitable openingor openings are provided for receiving the source(s) of radiation intothe lumen or compartment.

HDR after loaders useful for inserting the sources, with the aid of acarrier such for as, for example, a catheter, include those that havebeen designed for use with interstitial, intra-cavitary or intra-luminalbrachytherapy. The HDR after loader system (not shown) typicallyincludes a) a shielded container to house an intense radioisotope sourcewhen not in use, b) a delivery system to advance the sources from theshielded container through one or more compartments, channels or lumens,with the aid of the carrier, e.g., catheters or like structures, inplace with respect to the patient in the desired area of treatment andc) a control system which monitors and controls the dwell position andtime of the sources within the treatment carrier to assure that the dosedelivered matches the dose prescribed. In the brassier applicator of thetype shown in FIGS. 3 and 4, using the lumens for source placement, thedose to the underlying tissues is controlled by adjusting the dwellposition and dwell time. Further, in this embodiment, one or more fieldshaping cells prepositioned in the lumen can be used or positioned inrelationship to the source(s) so that they coincide with the dwellpositions of the sources. Alternatively, a continuous aperture along thelumen may be employed for controlling the dose to a designated volume toreduce the relative dose to the skin or healthy tissues such as theheart, lungs or contralateral breast.

In the case of the present disclosure, it is further contemplated thatthere be the option of a control system, preferably including a computerprogram arranged so as to control the dwell position of the source(s)within the lumen(s) of the applicator.

The control system preferably will require parametric inputs, bothstatic and dynamic, which can include geometrical factors (source size,shape, applicator size and shape and others), dose prescription factors(dose, dose rate, target tissue and others), biological factors (targettissue, margins, sensitive tissue locations and others), source factors(size, shape, activity, activity distribution) and dynamic factors(patient and operator readiness, proper mechanical positioning andoperation verification, position telemetry and others) to provideprocess/procedure control. The control system may also include optionsfor user intervention, overrides, monitoring, and reporting.

A computer program may be used in the treatment planning process. Thisprogram will offer the option of (a) defining the dose distribution tothe protruding organ, or to a designated targeted volume within theorgan, and (b) determining an appropriate distribution of source(s),field shaping cells and/or dwell times along the periphery of the organ.The computer program could also allow the user to define the source(s)and/or field shaping cells and their locations, and calculate the dosedistribution within the organ. In any case, the program may accept oneor more of the following parametric inputs: the number, type, species,intensity, shape, activity distribution, size, etc. in determining therequired placement of, or resulting dose distribution from the sources.Further, the number, type and characteristics of field shaping cells, ifused, may be included in the determination. The treatment planningsoftware program may include the option of enabling the alignment of thecoordinate systems of the treatment planning software with that of theprotruding organ, applicator or imaging system. The use of the markerson/within the applicator along with either reference anatomicallandmarks or applied imagable markers on or within either the protrudingorgan or the applicator may be used by the program to facilitate theoverlay of the coordinate systems of the software program and one ormore of the following: the organ, the applicator and the imaging system.Alternately, the position of the target tissue may be determined by animaging modality that is directly incorporated into, or in communicationwith, the treatment system that provides input data to the computerprogram. Multidimensional images of the organ and associated structuresmay be imported by the software program to facilitate this alignment.Options to calculate the placement of sources based on a combination ofdose to the designated volume and a dose limitation to neighboringorgans or tissues may be included. The software program may also includethe option of real-time feedback on dose delivered to the targetedtissue where the future source positions and dwell times arerecalculated as often as desired based on the historical dose deliveryfeedback.

The radioisotope(s) may be transmuted within the source carrier (e.g. bydirect nuclear activation) or may be dispersed into, or applied to, thesurface of carriers by any number of chemical or physical methods,simple adhesion or encapsulation. Examples of some of the more commonmethods include the processes of plating, painting, sputtering, reactionbonding, encasement of radioisotope dispersion within a polymer and thelike. Other methods may also be employed.

The radionuclide(s) of the source(s) could be chosen from the list ofcommonly recognized and/or available radionuclides. The ideal isotopehas the right combination of half-life, gamma ray energies and ease ofproduction and purification. The half-life has an impact on the shelflife of the product. The x-ray or gamma ray (photon) energies controlthe depth of the field for dose delivery and may be optimized such thatit matches the volume and location of the tumor bed. Higher energyphotons are better for more deeply seated targets. Finally, theradionuclide must be chosen among available or easily produciblespecies. The primary current options for radioisotopes capable ofmeeting these requirements include, but are not limited to Co-56, Co-57,Co-58, Co-60, Zn-65, Pd-103, Cd-109, 1-125, Cs-131, Cs-137, Sm-145,Gd-153, Yb-169, W-187, Ir-192, and Au-198, though other sources can, andin the future may, meet these criteria. To treat organs of the generalsize as defined in this application, the energy of the primary photonemissions should be limited to the range of between about 20 KeV andabout 1500 keV. For the breast, the energy of the primary emissions ofpreferred sources are preferably generally between about 50 keV andabout 1300 keV.

The radioactive source(s) contemplated in this disclosure can begenerators of ionizing radiation, delivering a diverging exposure field,such as x-ray sources or electron sources that can be placed peripheralto the protruding organ. An example of the radiation source is anorthovoltage x-ray source. The dwell position of the generators and theintensity of the emissions can be controlled to deliver the desiredtherapeutic dose to a target volume within a protruding organ as aresult of the superposition of the fields from the individual sourcedwell positions. Field shaping structures, as described earlier, can beadded to the generators to shape the exposure field.

The current brachytherapy applicator is different from previousapplicators as it is suitable for treatment of a large designated volumewithin a protruding organ. It requires at least one divergent beam fromat least one radiation source placed within an applicator mounted on thesurface of a protruding organ. The applicator is affixed to the organand provides a stable platform for receiving the radiation source(s) anddelivering the dose to the designated volume independent of the targetmovement (e.g., due to the breathing cycle). The designated volume aswell as the applicator are initially identified by imaging guidance forproper alignment and monitoring of the dose. The source must be within anarrow range of distance from the skin. Placing the source too close tothe skin (less than about 3 mm) results in excessive skin exposure;while placing the source farther than about a few cm (e.g., 5 cm) awayfrom the skin results in the intensity falling off, the range ofallowable frontal exposure angles being restricted and the brachytherapybecomes inefficient. The overlap of the divergent beams where theexposure fields are superpositioned provides the therapeutic dose whilethe portion of volume that is not exposed to the intersection of thedivergent beams receives a sub-therapeutic dose.

It should be appreciated that the distributive effect can be achieved bya single extended or multiple segmented sources and single or multiplefield shaping cells. In the case of a single extended source, the singlesource is configured to extend over an area so as to radiate fromdifferent directions or angles toward the targeted tissue or designatedvolume such that the radiation field from one portion of the source issuperpositioned upon the field generated from other portions of the samesource so as to constructively overlap and provide the desired dose tothe targeted tissue or designated volume. By creating a proper radiationpattern, the method and product allow for a higher concentration ofradiation to be delivered non-invasively to the targeted tissue ordesignated volume than a source which delivers radiation from a singlepoint source or from a source where radiation is emitted at one position(a planar or a line source), while reducing the exposure of surroundingtissue to incidental radiation.

FIG. 5 shows an example of embedded field shaping structure (with one ormore apertures) within an applicator to facilitate directional deliveryof radiation, and achieve the desired overlap, or superposition, ofradiation patterns in predetermined volume of interest. As seen in thedrawing, the illustrated embodiment includes attenuating material thatis preferably a part of the applicator. The attenuating material 70 ispreferably provided with a plurality of channels 72 within theattenuator. The source(s) 74 are preferably embedded in the respectivechannels so as to form directional diverging beam patterns 76. Thesource(s) 74 are positioned relative to the target area 78 so that thepatterns 76 overlap each other in the target area 78 so that so that ahigher dose of radiation is delivered to the target area 78 than thesurrounding areas.

FIGS. 6A-6D show the elements of a non-invasive peripheral breasttreatment using a parallel plate applicator approach. FIG. 6A shows theinitial imaging of the breast using a standard mammographic technique.In FIG. 6B, the location, size and shape of the lesion 80 are convertedto a treatment plan involving treatment from two substantiallyorthogonal directions 82 and 84, any where from 60 to 120 degrees fromthe original orientation. Each plate can define a plurality ofindividual source locations (as illustrated for example in FIG. 8B). InFIG. 6C the first treatment is delivered by a series of HDR source dwellpositions within each of the treatment applicators the direction 84. InFIG. 6D, the next treatment fraction is provided at a 90 degree anglewith respect to the first treatment fraction in the direction 82.Additional treatment fractions would be performed until the entiretherapeutic dose to the target tissue is achieved. In one embodiment,the follow steps are followed in order to apply radiotherapy to abreast. The method of application comprises:

-   -   A. Compressing the breast between two plates so as to define the        initial treatment plane;    -   B. Imaging the breast in the initial treatment plane while it is        immobilized to identify the designated volume of tissue in need        of radiotherapy;    -   C. Delivering radiotherapy divergent radiation to the designated        volume while the breast is immobilized from a direction within        an angle of 30 degrees from normal to the initial treatment        plane;    -   D. Removing the compression plates and rotating the compression        plates to a new orientation which is within 60 to 120 degrees of        the initial treatment plane, and re-applying compression to        immobilize the said protruding organ at the new orientation;    -   E. Identifying the designated volume by imaging, or other means,        within the protruding organ from the new orientation;    -   F. Delivering radiotherapy to the designated volume while the        protruding organ is immobilized in the new orientation from a        direction substantially normal to the compression plates; and    -   G. Repeating steps D to F, as needed until a therapeutic dose is        delivered to the designated volume within the protruding organ.

It should be apparent that while the embodiment described in connectionwith FIGS. 6A-6D employ two orientations of the compression plates, thetechnique could employ more than two orientations, depending on theapplication and/or desired treatment.

FIG. 7 illustrates an example of a cross-sectional isodose map overlaidonto a CT image from a prototype brassier-style applicator mounted on aphantom 121 to show the isodose distribution generated by an HDR sourcepattern. That portion of the source dwell positions along the peripheryof the breast which fall in this plane are highlighted as points 120.The isodose contours 122 indicate a typical uniformity pattern that canbe generated from this source distribution structure.

FIGS. 8A and 8B illustrate an example of using finite element analysis(FEA) of the field distribution from a single field shaping cell in FIG.8A, and a series of field shaping cells placed within the top and bottomplates of a parallel plate applicator in FIG. 8B. In FIG. 8A the2-dimension field distribution can be determined by finite elementanalysis for a field shaping cell. In the example shown the cell has anincluded angle of 90 degrees and a lead attenuator thickness of 9 mm.The angle and thickness can clearly vary depending on the particularcircumstances of treatment. This structure creates an unattenuatedfrontal radiation exposure field 130 and a substantially attenuated sideexposure field or zone 132. In FIG. 8B, an example of the impact of thisfield shaping structure on the 2-dimensional field uniformity betweenthe plates of a parallel plate applicator is shown. In this depiction,thirteen HDR catheter lumens 134 are placed in parallel and spaced 1 cmapart along the top plate 136 and bottom plate 138. The resultant fielduniformity is plotted.

FIG. 9 is a typical program flowchart indicating primary calculations,major inputs (both static and dynamic) and major decision-making paths.As shown in FIG. 9, various user or operator inputs include doseprescription factors 150, including dose, duration, dose rate, targetvolume, and fractionation; geometry factors 152, including shape of thetarget volume, size of the target volume, form of applicator, sourcelocations within the applicator, source path within the applicator;biological factors 154, including target tissue, margin definition,tissues sensitive to dose (i.e., any “no” treatment areas); and sourcefactors 156, including source shape, source activity distribution,source activity, and source flexibility. The various operator inputs areprovided to the program input of the program path, indicated at step160. Step 160 includes calculating the dose per fraction, dwell times,dwell positions, lumen selection and current dose rates. The results arethen presented to the operator as indicated at step 162 forconfirmation. The operator can override and revise the calculated doselevels based upon empirical determinations. Once the dose levels areset, the treatment can commence, as indicated at step 164. Dynamicinputs relating to the source, equipment and patient status are thenconsidered (indicated at step 166). These dynamic inputs include patientcondition, source position feedback verification, source movementmechanism, operator condition, and program error detection algorithm.These dynamic inputs are provided at step 168 where the source isadvanced (placed) in the starting position, and such positioning isconfirmed. At step 170, the decision is made whether the treatment ateach position is proceeding correctly. This is accomplished by accessingthe state of the target tumor(s) in light of the treatment carried outso far. If the starting position of the source cannot be confirmed atstep 168, or the treatment is proceeding incorrectly, the step proceedsto step 172 to an error handling module which assesses the problem inlight of the dynamic inputs 166. If on the other hand the decision atstep 170 is yes, a determination at step 174 is made whether theprescribed dose has been attained. If no, step 170 is repeated. If yes,a determination is made at step 176 as to whether the treatment is inthe final position. If yes, at step 178 the source is removed and adetermination is made as to as to whether the source is safe. If no, atstep 180 treatment is advanced to the next position, and in turn step170, and subsequent steps following step 170 are repeated for the nextposition.

Referring again to step 172, once the error handling module determinesthe error in treatment, a determination is made at step 182 whether theerror can be corrected. If yes, a correction or repair plan isdetermined and the treatment parameters revised at step 184. Adetermination is made at step 186 as to whether approval for the revisedtreatment parameters is needed. If not, step 180 and the subsequentsteps are repeated. If yes and approval is obtained, at step 188, step180 and the subsequent steps are repeated. If no, step 178 and thesubsequent steps are repeated. Finally, at step 178 the source(s) areremoved and the source(s) are verified as safe, reports are produced, asindicated at step 190, and the treatment is ended, as indicated at step192. It should be appreciated that many of the procedural steps of theflow chart described in connection with FIG. 9 can be implemented bysoftware and stored in suitable memory, such as a CD or ROM of acomputer, and operated by the operator on a desktop, laptop, workstationor other similar system.

FIG. 10 is a demonstration of the use of field shaping cells incombination in a HDR procedure. As the example shown, an HDR catheterlumen 200 includes one or more field shaping cells 202, including a HDRsource of radiation 204, fixedly attached to or movable within thecatheter lumen 200. As shown, the cell 202 and source 204 provide adiverging beam of radiation toward the targeted volume 206. As seen, thefield shaping cells can be prepositioned in the prescribed locations forthe desired treatment. In this instance a single HDR source 204 can befirst advanced so as to move the source 204 through successive cells sothat the source 204 is allowed to dwell for a predetermined time at aposition within the field shaping cell 202 to deliver a predeterminedpartial dose from each cell. The process is repeated by advancing theHDR source 204 to each successive position 210 for the prescribed timeof exposure. The number of positions and locations is dependent on theparticular treatment. Use of field shaping cells limits the sideexposure of the dose to the surrounding, superficial tissue (adjacent tothe skin) while at the same time allowing accumulation of a larger doseto the predetermined target volume within that organ.

FIG. 11 demonstrates how the orientation of the field shaping cells 216can be used to control the exposure of tissues to radiation. In FIG. 11Athe field shaping cells 216 are oriented perpendicular to the chestwall, treating the breast uniformly, but allowing exposure to positionsbelow the chest wall 217. In FIG. 11B, the field shaping cells 216 areoriented away form the chest wall and thus minimize the dose topositions below the chest wall 217 so as to create a chest wall sparingorientation.

The same results are achieved by using a continuous aperture along thepath of the radiation source as show in FIG. 12. Referring to FIG. 12,an embodiment of a continuous field shaping structure is shown asincluding an unimpeded frontal open angle 220, a longitudinal axis 222the aperture 224, a radiation attenuator structure 226, such as acatheter containing a radiation absorption material, the lumen 228 forthe radiation source, such as either the HDR source or the X-raygenerator, the surface 230 of the extended applicator, the surface ofthe breast 232, the space 234 for the intermediate skin contacting layerbetween the applicator and the breast surface and the direction of theunimpeded frontal exposure 225.

FIG. 13 shows the elements of an embodiment of a single radiation fieldshaping structure 250 for creating a diverging beam defined radiationexposure field. Structure 250 includes the radiation absorption materialdefining an opening 252, preferably but not necessarily conical inshape, defining a frontal open angle 254 (and defining a half angle 256)and aperture 258, the source 260 positioned relative to the aperture 258by the height or set-back distance 262, and an attenuator 264. The beamof radiation emanating from the source 260 through the aperture 258 isdefined by a centerline or beam axis 266, and thus defines the divergentfrontal exposure field 268 and the side exposure direction/zone 270.Through variation of open angle 254, half angle 256, aperture 258,distance 262, the divergent exposure field emitted from the fieldshaping structure 250 can be limited and facilitate the proper overlapof multiple divergent exposure fields with the size, shape and locationof the lesion within the protruding organ.

FIG. 14 shows an alternate embodiment of an applicator, utilizing arobotic based applicator. The radiation source 270 is mounted on an arm272, which in turn is mounted in a support 274 and adapted to rotateabout a rotation axis 276. In this arrangement the breast 278 issuitably positioned relative to the application, as for example, allowedto hang by force of gravity through an aperture 280 formed in a patientsupport 282. Shown are the rotational angle 284, the azimuthal angle286, source tilt angle 288, source distance variation 290, heightvariation 292 and lateral displacement 294 of the support 274 relativeto the breast 278. The rotational angle 284, azimuthal angle 286, sourcetilt angle 288, source distance variation 290, height variation 292 andlateral displacement 294 define the six degrees of freedom, and operatein concert to allow the PBB technique to properly align the source(I)(oralternately source and field shaping structure) and source direction atany point along the periphery of, but at a close distance to (within thedimensions previously mentioned) or in direct contact with the breast soas to allow proper tracking or alignment of the divergent exposure fieldfrom the radiation source with the designated volume 296 within thebreast.

Referring to FIGS. 15A-C, the relationship is demonstrated between theplacement of the source or generator of radiation within a field shapingstructure and the resultant radiation field. FIG. 15A shows a fieldshaping structure 298 with a radiation source 300 placed centered andnear the aperture generating a broadly divergent radiation field 302.FIG. 15B shows a field shaping structure 298 with the radiation source300 centered and near the aperture generating a broadly divergentradiation field pattern 302. Finally, FIG. 15C shows a field shapingstructure 298 with radiation source 300 placed “off-center” and awayfrom the aperture in the field shaping structure generating a narrowedand asymmetric divergent radiation field 306.

Various additional aspects of the disclosed system and method:

The applicator can custom designed for single patient use. For treatmentof the breast, the radiation distribution pattern can be designed sothat the dose to the nipple and/or the dose to the excision site iscontrolled (reduced or increased) as desired. The applicator can includeradiation monitor(s) to track/measure the superficial (skin) dose. Inthose embodiments where the applicator has an inner skin contactinglayer, the space between the surface of the breast and the applicatorprovides a controlled separation distance between the source and theskin. In addition, the inner skin contacting layer of the applicator canbe separable from the applicator. In one alternative arrangement, theapplicator can include an intermediate layer comprising a high watercontent or water equivalent material including, but not limited to awater filled sponge, balloon or gel media.

It is envisioned that the primary radioisotope should include a dominantgamma-ray energy somewhere between about 20 and about 1500 keV, andpreferably dominant energy somewhere between about 50 and 1300 keV. Theradioisotope is preferably selected from a group including; Co-56,Co-57, Co-58, Co-60, Zn-65, Pd-103, Cd-109, 1-125, Cs-131, Cs-137,Sm-145, Gd-153, Yb-169, W-187, Ir-192, and Au-198. In one embodiment theradiation source is an orthovoltage x-ray source. The dose can bedelivered either continuously or intermittently (by fractions) over aperiod ranging from between about 10 minutes to about 60 days. It isalso envisioned that the radiation dose in each fraction is betweenabout 1 and about 10 Gy and the accumulated dose is in the range ofbetween about 10 to about 100 Gy. The dose to the designated volumeduring each fraction is preferably between about 3.0 and about 4.0 Gy,and a total dose of between about 30 to about 40 Gy delivered in 8 to 10sessions over a period of 4-5 days. The non-invasive brachytherapy canbe applied intermittently until the prescribed fractionated dose isdelivered in each session. The non-invasive brachytherapy describedherein can be performed as a boost to other radiotherapy procedures. Forexample, the non-invasive brachytherapy technique can be combined withhyperthermia, radiation sensitizers or other means of enhancing theeffectiveness of the radiation treatment. It should be evident that thedose and treatment can vary. Where the accumulated therapeutic radiationdose delivered is in the range of between about 15 to about 45 Gy, it ispreferred that the average subtherapeutic dose delivered to surroundingtissue is at least 20% lower than the therapeutic dose. As previouslystated, the source can be applied while the patient is in a proneposition, or in a supine position. Alternatively, the source can beapplied while the patient is sitting or standing. the applicatorcontains field shaping structures to allow substantially unimpededdivergent frontal exposure to the breast tissue while limiting the sideexposure of the superficial breast tissue to decrease the skin dose.

The applicator preferably includes field shaping structure used tocreate a divergent exposure field. The field shaping structure, made ofa radiation absorptive material, such as lead, preferably comprises anaperture with an opening angle extending at least about 20 degrees(half-angle from normal incidence of 10 degrees) but not more than about150 degrees (half angle from normal incidence of 75 degrees) reducingthe side radiation exposure (on the average) by at least 30%. In thecase of treatment of the breast, the radioactive source(s) is (are)placed within side exposure limiting structures of the applicator, suchas suitably shaped apertures so that the axis of the divergent frontalexposure field is oriented away from the chest wall as to reduce thestray dose to the heart and lungs. In such an application, the openangle of the unimpeded frontal exposure is less than about 150 degreesin at least one plane. In the embodiment where a HDR source is used withthe applicator for treatment of the breast, an extended axial aperturestructure is used around the HDR source axial path to allow the freepassage of the divergent radiation in the frontal direction whilelimiting side exposure thus reducing the relative dose to the skin ascompared to the designated breast tissue dose. The depth of an extendedaxial aperture channel such as the shown in FIG. 12, can allow thepassage of a HDR source and allow the distance of the HDR source fromthe aperture channel to be varied so that the distance will determinethe divergence of the exposure field. Field shaping structures includeapertures, masks, shutters, field shaping cells, bands, grooves, orattenuating sheaths and spacers of fixed or variable geometries.

When treatment planning software, such as that described in connectionwith FIGS. 9A and 9B, the radiation exposure parameters such as isodosecenter, dose volume and dose uniformity are based on the size and shapeof the breast or the size, shape and volume of the tumor, tumor bed. ora designated volume within the breast. Preferably, the radiationexposure parameters such as isodose center, dose volume and doseuniformity are designed to match the designated dose and dosedistribution with the size and shape of the breast or the location andextent of the tumor or tumor bed within the breast, as identified fromimage guidance. The dose is preferably referenced to dose referencepoints within the breast identified from appropriate image guidance. Theposition, intensity, size, shape, energy of the source or sources arepreferably chosen such that the radiation treatment volume coincideswith the size and shape of the breast or the size, shape and location ofthe tumor, tumor bed or other designated volume within the breast basedon image guidance. The dwell position, dwell pattern, and dwell time, ofthe HDR source is chosen such that the radiation treatment volumecoincides with the size and shape of the breast or the size, shape andlocation of the tumor or tumor bed as identified by image guidance. Forpurposes of treatment, imagable markers within the applicators are usedfor alignment of the position of the applicator to the breastcoordinates to coincide the radiation treatment volume to tumor or tumorbed volume. The treatment planning software preferably allows the doseto the treatment volume to be monitored in real-time so as to controlthe dwell position(s) and dwell time(s) of the source(s). Theradioactive sources are encapsulated in a carrier which takes the shapeof a point source, wire, tube, or foil, or may be loaded or embeddedinto a carrier by means of painting, plating, mixing into a dispersion,and chemical or physical bonding within or on the surface of a carrier.The sources can be small pellets or extended sources in the form of aline (one-dimensional). The sources can be filtered (shielded) orextended sources in the form of a flat plane (two-dimensional). Thesources can be extended sources in the form of a curved plane (threedimensional). In one embodiment, the source(s) can traverse along aspiral trajectory along the periphery of the breast and extending fromthe chest wall to the nipple such as shown in FIGS. 3 and 4. In onealternative embodiment, the source(s) traverse multiple, co-axialcircular trajectories, all of which are largely parallel to the chestwall and are located along the periphery of the breast. In yet anotherembodiment, the source(s) traverse along curved radial lines extendingfrom nipple to the chest wall and are located along the periphery of thebreast. The sources may be small pellets or extended sources in the formof a line (one-dimensional). The sources may be filtered (shielded) orextended sources in the form of a flat plane (two-dimensional). Orfiltered (shielded) or extended sources in the form of a curved plane(three dimensional).

While certain embodiments have been described of an apparatus and methodthat provide brachytherapy, it is to be understood that the conceptsimplicit in these embodiments may be used in other embodiments as well.The protection of this application is limited solely to the claims thatnow follow.

In these claims, reference to an element in the singular is not intendedto mean “one and only one” unless specifically so stated, but rather“one or more.” All structural and functional equivalents to the elementsof the various embodiments described throughout this disclosure that areknown or later come to be known to those of ordinary skill in the artare expressly incorporated herein by reference, and are intended to beencompassed by the claims. Moreover, nothing disclosed herein isintended to be dedicated to the public, regardless of whether suchdisclosure is explicitly recited in the claims. No claim element is tobe construed under the provisions of 35 U.S.C. §112, sixth paragraph,unless the element is expressly recited using the phrase “means for” or,in the case of a method claim, the element is recited using the phrase“step for”.

1. A method of non-invasively delivering brachytherapy to a designatedvolume within a protruding organ, comprising: a. Identifying adesignated volume within the organ in need of radiation treatment, anddetermining locations at or near the periphery of the organ from whichan enhanced dose of divergent radiation can be transcutaneouslydelivered to the designated volume of the protruding organ so that ahigher dose is delivered to the designated volume than to tissuesurrounding the designated volume; b. Employing image guidance to locatethe designated volume; c. Securing a non-invasive applicator to theorgan so that the applicator can receive and fixedly position at leastone radiation source relative to the designated volume; and d. Exposingfor a predetermined amount of time the designated volume at each of thedetermined locations at or near the periphery of the organ so that atherapeutic dose is delivered to the targeted volume and asub-therapeutic dose is delivered to the targeted volume and asub-therapeutic dose is delivered to tissue surrounding the designatedvolume.
 2. A system for non-invasively delivering brachytherapy to adesignated volume within a protruding organ, comprising: a. an imagingsystem constructed and arranged so as to (a) Identify a designatedvolume within the organ in need of radiation treatment, (b) aid in thedetermination of locations at or near the periphery of the organ fromwhich an enhanced dose of divergent radiation can be transcutaneouslydelivered to the designated volume of the protruding organ so that ahigher dose is delivered to the designated volume than to tissuesurrounding the designated volume; and (c) assist in the employment ofimage guidance to locate the designated volume; b. a non-invasiveapplicator shaped so that the applicator can be fixed relative to theorgan, the applicator being constructed and arranged so that theapplicator can receive and fixedly position at least one radiationsource relative to the designated volume; expose for a predeterminedamount of time the designated volume at each of the determined locationsat or near the periphery of the organ so that a therapeutic dose isdelivered to the targeted volume and a sub-therapeutic dose is deliveredto the targeted volume and a sub-therapeutic dose is delivered to tissuesurrounding the designated volume.
 3. A method of applying brachytherapyto a protruding organ, comprising: placing a non-invasive applicator onthe organ, the applicator constructed and arranged so as to receive atleast one radiation source and expose a designated volume within theorgan from at least two dwell positions; controlling the dwell positionand the dwell time of the radiation source placed via the applicator ata close distance to the periphery of the organ such that the divergingexposure field from each dwell position is superpositioned on thediverging exposure field from other dwell positions to deliver atherapeutic dose to a large portion or substantially the entire volumeof the said organ.
 4. A system for applying brachytherapy to aprotruding organ, comprising: a non-invasive applicator configured tocontact the organ during treatment, the applicator constructed andarranged so as to receive at least one radiation source and exposetranscutaneously a designated portion of the organ from at least twodwell positions; and controlling the dwell time of the radiation sourceat each of the dwell positions placed via the applicator at or near theperiphery of the organ such that the diverging exposure field from eachdwell position is superpositioned on the diverging exposure field fromother dwell positions to deliver a therapeutic dose to a targeted volumewithin the organ.
 5. The method of applying brachytherapy to adesignated volume within a protruding organ: using image guidance tolocate the designated volume; placing on the organ a non-invasiveapplicator with at least one radiation source so that the designatedvolume can be exposed transcutaneously for a predetermined dwell timefor each of at least two dwell positions at or near the periphery of theorgan; and controlling the dwell position and the dwell time of theradiation exposure at each of the dwell positions such that thediverging exposure field from each dwell position is superpositioned onthe diverging exposure field from other dwell positions to deliver atherapeutic dose to the designated volume and a sub-therapeutic dose toother tissue adjacent the designated volume.
 6. The system for applyingbrachytherapy to a designated volume within a protruding organ: animaging system for defining the designated volume; a non-invasiveapplicator with at least one radiation source constructed to be placedon the organ so that the designated volume can be exposedtranscutaneously for a predetermined dwell time for each of at least twodwell positions at or near the periphery of the organ; and control thedwell position and the dwell time of the radiation exposure at each ofthe dwell positions such that the diverging exposure field from eachdwell position is superpositioned on the diverging exposure field fromother dwell positions to deliver a therapeutic dose to the designatedvolume and a sub-therapeutic dose to other tissue adjacent thedesignated volume.
 7. A method of applying radiotherapy to a protrudingorgan, comprising: A. Compressing the protruding organ between twoplates so as to define the initial treatment plane; B. Imaging theprotruding organ in the initial treatment plane while it is immobilizedto identify the designated volume of tissue in need of radiotherapy; C.Delivering radiotherapy to the designated volume while the protrudingorgan is immobilized from a direction within an angle of 30 degrees fromnormal to the initial treatment plane; D. Removing the compressionplates and rotating the compression plates to a new orientation which iswithin 60 to 120 degrees of the initial treatment plane, and re-applyingcompression to immobilize the said protruding organ at the neworientation; E. Identifying the designated volume by imaging, or othermeans, within the protruding organ from the new orientation; F.Delivering radiotherapy to the designated volume while the protrudingorgan is immobilized in the new orientation from a directionsubstantially normal to the compression plates; G. Repeating steps D toF, as needed until a therapeutic dose is delivered to the designatedvolume within the protruding organ.
 8. The method of claim 7, where theprotruding organ is the breast.
 9. The method of claim 8, wherein thebreast has been subjected to a lumpectomy procedure and wherein thedesignated volume is the lumpectomy cavity margin.
 10. The method ofclaim 7, comprising the means of compression, imaging and deliveringradiation therapy are performed with a single apparatus.
 11. Anapparatus for applying radiotherapy to a protruding organ, comprising:A. a pair of plates constructed and arranged so as to compress theprotruding organ and define an initial treatment plane, wherein thecompression plates are adapted to rotate to at least a secondorientation, and re-applying compression to immobilize the saidprotruding organ at the new orientation; B. an imaging deviceconstructed and arranged so as to image the protruding organ in theinitial treatment plane while the organ is immobilized and so as toidentify the designated volume of tissue in need of radiotherapy, andidentify the designated volume in the second orientation; C. a radiationdelivery system constructed and arranged so as to deliver radiotherapyto the designated volume while the protruding organ is immobilized froma direction within an angle of 30 degrees from normal to the initialtreatment plane.
 12. The system according to claim 11, wherein thesecond orientation is within 60 to 120 degrees of the initial treatmentplane.
 13. The system according to claim 11, where the protruding organis the breast.
 14. The system according to claim 13, wherein the breasthas been subjected to a lumpectomy procedure and wherein the designatedvolume is the lumpectomy cavity margin.
 15. A system for applyingnon-invasive brachytherapy to a targeted volume within a conformableprotruding organ of a patient, comprising: an applicator constructed soas to be positioned relative to the organ so that an enhanced dose ofdivergent radiation is deliverable from at least two locations at orvery near the periphery of the conformable protruding organtranscutaneously to the targeted volume of the conformable protrudingorgan from at least two directions so that a higher dose is delivered tothe targeted volume than to tissue surrounding the targeted volume;treatment planning program used to guide the use of the applicator; andan image guidance device constructed and arranged so as image thetargeted volume wherein the treatment planning program and imageguidance device is sued to determine the optimum treatment plan.
 16. Asystem according to claim 15, wherein the treatment planning programincludes parameter determination subprogram configured and arranged soas to determine radiation exposure parameters including isodose center,dose volume and dose uniformity as a function of the designated dose anddose distribution with the size and shape of the protruding organ andthe location and extent of the targeted volume, as identified from theimage guidance device.
 17. A system according to claim 16, wherein thetreatment planning program includes a subprogram configured and arrangedso as to determine the position, intensity, size shape, and energy ofone or more sources for providing the enhanced dose as a function of thetargeted volume, which in turn is determined by the size and shape ofthe organ, or the size and shape of the designated volume identifiedfrom the image guidance device.
 18. A system according to claim 17,wherein the treatment planning program includes a subprogram configuredand arranged so as to determine the dwell position, swell patter, anddwell time, of one or more sources for providing the enhanced dosecoincides with the targeted volume.
 19. A system according to claim 15,further including image markers arranged to align the position of theapplicator to coordinates of the organ to coincide radiation treatmentwith the targeted volume.
 20. A method of applying non-invasivebrachytherapy to a targeted volume within a conformable protruding organof a patient, comprising: positioning an applicator positioned relativeto the organ so that an enhanced dose of divergent radiation isdeliverable from at least two locations at or very near the periphery ofthe conformable protruding organ transcutaneously to the targeted volumeof the conformable protruding organ from at least two directions so thata higher dose is delivered to the targeted volume than to tissuesurrounding the targeted volume; using a treatment planning program toguide the use of the applicator; using an image guidance device to imagethe targeted volume so as to determine the optimum treatment plan.
 21. Amethod according to claim 20, wherein using the treatment planningprogram includes determining radiation exposure parameters includingisodose center, dose volume and dose uniformity as a function of thedesignated dose and dose distribution with the size and shape of theprotruding organ and the location and extent of the targeted volume, asidentified from the image guidance device.
 22. A method according toclaim 20, wherein using the treatment planning program includesdetermining by the size and shape of the organ, or the size and shape ofthe designated volume identified from the image guidance device; anddetermining the position, intensity, size shape, and energy of one ormore sources for providing the enhanced dose as a function of thetargeted volume.
 23. A method according to claim 20, wherein using thetreatment planning program includes determining the dwell position,swell patter, and dwell time, of one or more sources for providing theenhanced dose as it coincides with the targeted volume.
 24. A methodaccording to claim 20, further including using image markers arranged toalign the position of the applicator to coordinates of the organ tocoincide radiation treatment with the targeted volume.